Graphical Abstract:

Abstract:

Background: Lymphatic route is one of the prominent routes for improving the poor
bioavailability of the drugs which undergo extensive hepatic first pass metabolism. Nanocarriers (solid
lipid nanoparticles) offer a new drug delivery system that could hold great promise for attaining the
bioavailability enhancement along with controlled and site specific drug delivery.

Objective: The aim of the present research work was to prepare and optimized the Quetiapine fumarate
(an antipsychotic drug) loaded solid lipid nanoparticles for lymphatic targeting through intraduodenal
administration.

Method: Thirteen quetiapine fumarate loaded solid lipid nanoparticle formulations were developed
using different lipids by Microemulsion technique and optimized by box behnken design.

Results: Optimized formulation (Q9) had a mean particle size of 230.38 nm with 75.92% of entrapment
efficiency. The percentage drug release after 24 h was found to be 95.81%. A significant difference
(P<0.05) was found in the in vitro release data of optimized formulation as compared to marketed formulation.
In vitro release data of optimized formulation (Q9) was subjected to zero order, first order
and Higuchi model to evaluate the release kinetics. Higuchi model was found to be the best fitted
model with highest value of correlation coefficient (R2= 0.999). In vivo studies for optimized solid lipid
nanoparticles formulation and drug suspension were performed on male Wistar rats after intraduodenal
administration and several pharmacokinetic parameters were determined. AUC (0–∞) of optimized
formulation was significantly (P<0.01) more than that of drug suspension. Bioavailability of quetiapine
in solid lipid nanoparticles was 2.76 fold increased after intraduodenal administration as compared with
that of drug suspension.

Conclusion: On the basis of results of in vitro study, Q9 formulation was selected as optimized
formulation. It exhibited better bioavailability as compared to drug suspension. It can be concluded that
solid lipid nanoparticles are potential carrier for improving quetiapine bioavailability through lymphatic
delivery.

Abstract:Background: Lymphatic route is one of the prominent routes for improving the poor
bioavailability of the drugs which undergo extensive hepatic first pass metabolism. Nanocarriers (solid
lipid nanoparticles) offer a new drug delivery system that could hold great promise for attaining the
bioavailability enhancement along with controlled and site specific drug delivery.

Objective: The aim of the present research work was to prepare and optimized the Quetiapine fumarate
(an antipsychotic drug) loaded solid lipid nanoparticles for lymphatic targeting through intraduodenal
administration.

Method: Thirteen quetiapine fumarate loaded solid lipid nanoparticle formulations were developed
using different lipids by Microemulsion technique and optimized by box behnken design.

Results: Optimized formulation (Q9) had a mean particle size of 230.38 nm with 75.92% of entrapment
efficiency. The percentage drug release after 24 h was found to be 95.81%. A significant difference
(P<0.05) was found in the in vitro release data of optimized formulation as compared to marketed formulation.
In vitro release data of optimized formulation (Q9) was subjected to zero order, first order
and Higuchi model to evaluate the release kinetics. Higuchi model was found to be the best fitted
model with highest value of correlation coefficient (R2= 0.999). In vivo studies for optimized solid lipid
nanoparticles formulation and drug suspension were performed on male Wistar rats after intraduodenal
administration and several pharmacokinetic parameters were determined. AUC (0–∞) of optimized
formulation was significantly (P<0.01) more than that of drug suspension. Bioavailability of quetiapine
in solid lipid nanoparticles was 2.76 fold increased after intraduodenal administration as compared with
that of drug suspension.

Conclusion: On the basis of results of in vitro study, Q9 formulation was selected as optimized
formulation. It exhibited better bioavailability as compared to drug suspension. It can be concluded that
solid lipid nanoparticles are potential carrier for improving quetiapine bioavailability through lymphatic
delivery.